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THE ROLE OF ROSUVASTATIN ON

DYSLIPIDAEMIA

Dr. Juwanto, SpPD. K-KV-FINASIM


Global burden of CVD due to atherosclerosis

Figure : Age-standardized deaths due to cardiovascular disease (rate per 100,000), 2004

Kelly et al., 2010. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. National Academies Press (US);
Burden of CVD in Asia

1. http://www.pace-cme.org/d/175/cv-risk-and-lipids-in-asia Accessed 14th march 2014


New Paradigm: Multi-Risk Factor Approach

Traditional CVD New CVD risk New targets and


perspective Hypercholesterolemia perspective goals for therapy

DM
Gender
Age Reduction of
Diabetes

total CVD risk


HTN

Hyper- HTN
cholesterol- is the primary
emia
goal
Organ
damage

Smoking

Multiple independent
Integrated identification and management of risk factors
risk factors (silo approach)
contributing to CVD risk
(global approach)
CVD: Cardiovascular disease;
DM: Diabetes mellitus; HTN: Hypertension
Volpe M, et al. J Human Hypertens. 2008;22:154–157.
LDL Cholesterol
is
The Primary Target

in Dyslipidemia Treatment

NCEP ATP III 2003/ NCEP ATP III Update 2004


ADA/ACC Guideline Update for Secondary Prevention 2006
ESC/EAS Guidelines for the management of Dyslipidemias 2011
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults
Who is at Risks?
European Society of
Cardiology Guidelines1 ACC/AHA Guidelines2

• Documented CVD
• DM (type 1 or 2) with one or more CV risk factors and/or Patients with clinical ASCVD
Very high risk target organ damage
• Severe CKD
• A calculated SCORE ≥10%.

•Markedly elevated single risk factors Patients with primary elevation of LDL-C of >190 mg/dL
•DM (type 1 or 2) but without CV risk factors or target organ
High risk damage
•Moderate CKD
•SCORE of ≥5% and 10% for 10-year risk of fatal CVD
Patients with diabetes aged 40-75 years with LDL-C of 70-189 mg/dL without
clinical ASCVD
• Subjects are considered to be at moderate risk when
Moderate risk their SCORE is ≥1% and <5% at 10 years

Patients without clinical ASCVD or diabetes with LDL-C of 70-189 mg/dL and
estimated 10-year ASCVD risk of >7.5%
• The low risk category applies to individuals with SCORE
Low risk
<1%.

ACC, American College of Cardiology; AHA, American Heart Association; ASCVD, atherosclerotic cardiovascular disease ; CKD, chronic kidney disease; CV, cardiovascular; CVD,
cardiovascular disease; DM, diabetes mellitus; LDL-C, Low density lipoprotein- cholesterol; SCORE, Systematic Coronary Risk Evaluation Project.

1. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701.
2. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American
Heart Association Task Force on practice guidelines. 2013. Accessed December 16, 2013.
SCORE Chart: Assessment of Cardiovascular Risk Score

10-year risk of fatal CVD is based on risk


factors: Age, smoking, sex, systolic
blood pressure and total cholesterol.

SCORE, Systematic Coronary Risk Evaluation Project; CVD, cardiovascular disease

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701
Cardiovascular Risk Reduction: Recommendations of ESC
Guidelines
• Smoking Lifestyle modification
cessation
• Dietary
modification
• Weight Management of comorbid
management
• Physical activity conditions

Lipid-lowering drugs

ESC, European Society of Cardiology

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–1701
Lipid-Lowering Medications: Statins have maximum
benefit
Medication Effect on LDL-C Effect on HDL-C Effect on TG Effect on Lp(a)

Statin ↓↓↓ ↑ (also depends on ↓ ↔


statins)
Bile acid sequestrants ↓↓ ↔↑ ↑ ↔

Nicotinic acid ↓ ↑↑ ↓↓ ↓

Cholesterol absorption ↓↓ ↔ ↔ ↔
inhibitor

Fibric acid derivatives ↓ ↑ ↓↓↓ ↔

CIMT, carotid intima medial thickness; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp, Lipo protein; TG, Triglycerides

Jellinger PS , Smith DA, Mehta AE, et al. AACE Guidelines. American association of clinical endocrinologists' guidelines for management of dyslipidemia and prevention of
atherosclerosis. https://www.aace.com/files/lipid-guidelines.pdf. Accessed on December 3, 2013.
2013 ACC/AHA Guideline Recommendations for Statin Therapy

ASCVD Statin Benefit Groups


Heart healthy lifestyle habits are the foundation of ASCVD prevention

Diabetes; age 40-75 Estimated 10-yr ASCVD risk


Clinical ASCVD LDL-C ≥190 mg/dL
years* ≥7.5%†; age 40-75 years*

• High-Intensity statin (age ≤75 • High-intensity statin • Moderate-intensity statin • Moderate- to high-intensity
years) statin
• Moderate-intensity statin if • High-intensity statin if
• Moderate-intensity statin if not a candidate for high- estimated 10 year ASCVD risk
>75 years or not a candidate intensity statin ≥7.5%
for high-intensity statin

ASCVD prevention benefit of statin therapy may be less clear in other groups . Consider additional factors influencing ASCVD risk , potential ASCVD
risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment.

* With LDL-C of 70-189 mg/dL


† Estimated using the Pooled Cohort Risk Assessment Equations

Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at: http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed
November 13, 2013.
Intensity of Statin Therapy
High-Intensity Statin Therapy Moderate-Intensity Stain Therapy Low-Intensity Statin Therapy

LDL–C ↓ ≥50% LDL–C ↓ 30% to <50% LDL–C ↓ <30%

Atorvastatin (40†)–80 mg Atorvastatin 10 (20) mg Simvastatin 10 mg


Rosuvastatin 20 (40) mg Rosuvastatin (5) 10 mg Pravastatin 10–20 mg
Simvastatin 20–40 mg‡ Lovastatin 20 mg
Pravastatin 40 (80) mg Fluvastatin 20–40 mg
Lovastatin 40 mg Pitavastatin 1 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg bid
Pitavastatin 2–4 mg

Lifestyle modification remains a critical component of ASCVD risk reduction, both prior to and in concert with the use of cholesterol lowering drug therapies.

Statins/doses that were not tested in randomized controlled trials (RCTs) reviewed are listed in italics
†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL
‡Initiation of or titration to simvastatin 80 mg not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.

Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at: http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed November 13,
2013.
STATINS MECHANISM OF ACTION

Cholesterol Biosynthesis and the Beneficial and Adverse Downstream Effects of Statin Treatment Beneficial (gray background) and adverse (checkered background) downstream
effects of statin treatment. eNOS = endothelial nitric oxide synthase; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LPS = lipopolysaccharide; NAD(P)H = nicotinamide adenine
dinucleotide phosphate; NFκB = nuclear factor kappa B; PI3 = phosphatidylinositol-3; PP = pyrophosphate; tRNA = transfer ribonucleic acid. Important intermediate products in the
mevalonate pathway include the isoprenoids, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate.[1,2] These intermediate products lead to activation of various downstream
intracellular signaling molecules by prenylation of the guanosine triphosphate-binding proteins Rho, Ras, and Rac

http://www.medscape.com/viewarticle/569335_4, http://www.medscape.com/viewarticle/577060_2
PLEIOTROPIC
EFFECTS OF
STATINS
Effects beyond cholesterol
lowering
• improving endothelial function

• enhancing the stability of


atherosclerotic plaques
• decreasing oxidative stress and
inflammation
• inhibiting the thrombogenic
response.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694580/
http://content.onlinejacc.org/article.aspx?articleid=1136976
GUIDELINES

ROSUVASTATIN
CLINICAL STUDY

ROSUVASTATIN
PULSAR STUDY
Rosuvastatin 10
mg was more
efficacious than
atorvastatin 20
mg in reducing
LDL-C

Trials 2006, 7:35


http://www.trialsjournal.com/content/7/1/35
Rosuvastatin
10 mg was
significantly
more effective
than
atorvastatin
20 mg in
reducing LDL –
C level

Trials 2006, 7:35


http://www.trialsjournal.com/content/7/1/35
ARIES STUDY
Rosuvastatin 10
& 20 mg
improved overall
lipid profile of
hypercholesterole
mic African
Americans better
than did miligram
equivalent doses
of atorvastatin

Am J Cardiol 2006;97:229 –235


ARIES STUDY
RSV IMPROVED LIPID PROFILE

Rosuvastatin 10 & 20 mg improved overall lipid profile


of hypercholesterolemic African Americans better than did
miligram equivalent doses of atorvastatin
Am J Cardiol 2006;97:229 –235
Rosuvastatin 10 & 20
mg improved overall
lipid profile of
hypercholesterolemic
African Americans
better than did
miligram equivalent
doses of atorvastatin

Am J Cardiol 2006;97:229 –235


• Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were
recorded for rosuvastatin 5 mg and 10 mg.
Brewer. Am J Cardiol. 2003 Aug
21;92(4B):23K-29K.